Biology Reference
In-Depth Information
(8-10 months), the subsequent inter-relapse intervals were short (
Fig. 2.3
).
In fact, they were similar to the intervals from primary infection to early
relapse, which occurred in some Madagascar/St. Elizabeth phenotypes
and all Chesson phenotypes. The generally accepted theory to explain the
remarkable periodicity of vivax malaria relapses has been that 'sporozoite
populations of all strains of
P. vivax,
P. ovale
, and relapsing simian malarias
such as
P. cynomolgi
, include a subpopulation that completes development
promptly and is responsible for the early primary attack, and a group of
subpopulations that undergo partial development to the resting hypnozoite
stage. Subsets of these dormant pre-erythrocytic stages are preprogrammed
to resume development at different times and, via this built-in time clock,
evoke the sequence of relapses that characterize sporozoite-induced infec-
tions with the afore mentioned plasmodia' (
Schmidt, 1986
). However, it is
difficult to understand how multiple relapses could occur at regular inter-
vals with generally small inocula (median ∼ 5 hypnozoites) and a simple
clock mechanism. This remarkable efficiency suggests that some activation
or feedback mechanism must operate in addition. A recent suggestion is
that mosquito bites themselves might provide the trigger - perhaps by
parasite sensing of a mosquito protein (
Hulden and Hulden, 2011
) can-
not be reconciled with the similarity of latency periods in indigenous
peoples living in malaria endemic areas and the latency periods observed
in malaria therapy patients and returned soldiers (i.e. away from seasonal
mosquitoes and independent of season). There are relatively few recent
data on relapse patterns in frequent-relapse 'tropical' vivax malaria, but the
available evidence confirms the remarkable periodicity documented in the
volunteer studies with the 'Chesson strain' (
Pukrittayakamee et al., 2000
;
Pukrittayakamee et al., 2010
). Much of the early volunteer data with tropi-
cal 'strains' was confounded partly by slowly eliminated drug effects and
inoculations of unnaturally large numbers of sporozoites. Robert Coatney
realized this, and so in 204 sporozoite-induced infections with the Chesson
strain (
Coatney et al., 1950b
), he made detailed longitudinal observations
following a single infected mosquito bite (
Fig. 2.3
). The number of relapses
varied considerably. In the seven volunteers, who were not reinfected, the
median (range) number of relapses following a single bite was five (one
to nine) and 11 of the 39 relapses in this group (28%) occurred more
than 6 months after the initial infection. The interval from one relapse
to the next was remarkably similar but overall, the inter-relapse intervals
gradually lengthened. Importantly, there could then be very long intervals
between relapses (4 relapses occurred with preceding latencies exceeding
